The general objective is to characterize by pharmacological and biochemical methods the adrenergic receptors in selected sympathetically innervated tissues in order to improve our understanding of factors at the receptor level which regulate the responses of these tissues to various adrenergic drugs and to sympathetic nerve stimulation. Experiments will be carried out 1) to ascertain whether the simultaneous occurrence of more than one type of adrenergic beta-receptor in a single cell type - such as we have documented for guinea-pig tracheal smooth muscle - is a common phenomenon; 2) to elucidate the factors (e.g., environmental, hormonal, genetic) which control the variable ratio of beta 1- to beta 2-type receptors in the tracheal smooth muscle cells; (3) to reexamine whether postjunctional adrenergic alpha-receptors in different sympathetic effectors in the same species are all of a single type; 4) to investigate whether prejunctional alpha-receptors on adrenergic nerve terminals (which mediate a feedback inhibition of release of the neurotransmitter) can be differentiated pharmacologically from postjunctional alpha-receptors. Perfused and isolated organs and tissues (including smooth muscles of blood vessels and lung, and cardiac preparations) will be employed, some with sympathetic nerves attached. Characterization of receptors responsible for mediating a specific response in a given tissue will be carried out by determining with appropriate pharmacological procedures absolute or relative affinities and efficacies of selected agonists, and affinities of selected competitive antagonist, for the receptors. In studies on prejunctional alpha-receptors, measurements will be made of norepinephrine (or 3H-norepinephrine) released on nerve stimulation. Situations where more than one type of beta-receptor occur in a single cell type will be analyzed by appropriate testing both with competitive antagonists "selective" for either the beta 1-type or beta 2-type and with agonists also "selective" for one or the other type. In addition, we shall explore the possibility of applying radioactive ligand-binding techniques for quantification of one or more (Text Truncated - Exceeds Capacity)